TWI278317B - Antibiotic compositions and methods for using same - Google Patents

Abstract

Compositions including a quinolone component in an amount effective as an antibiotic when the composition is placed in a mammalian eye, and a carrier component in an amount effective to act as a carrier for the quinolone component are provided. The present compositions are substantially free of other components effective as preservatives. Preferably the quinolone component has fungistatic activity. In one very useful embodiment, the compositions include a NSAID component in an amount effective to reduce inflammation or pain when the composition is placed in a mammalian eye. Methods of using the present compositions, for example, to resolve microbial infections and/or to reduce inflammation and/or pain in a mammalian eye are included within the scope of the present invention.

Description

I278317 Ministry of Economic Affairs Intellectual Property Office Employees Consumption Cooperative Printed A7 V. INSTRUCTIONS (1) t BACKGROUND The present invention relates to antibiotic compositions and methods of using the same. More specifically, the present invention relates to treatments which are effective in use and which are capable of alleviating the risk of harmful side effects such as eye < A variety of different antibiotic ingredients are now used in the eye, for example, to control or numerate or prevent eye infections and the like. In addition, antibiotic ingredients such as rapamycin (10) ramycin have been suggested to be compatible with other substances, and (4) are non-steroidal anti-inflammatory preparations or NSAIDs. See, for example, U.S. Patent Application Serial No. 5,414,011, the entire disclosure of which is incorporated herein by reference. The inclusion of one or more additives as a preservative, for example, gasified benzhydrylamine (BAK) or organic mercury. :,:: The use of BAK, organic fruit or other preservative ingredients may be problematic. For example, BAK may Incompatible with certain active ingredients, organic extraction is difficult due to its strong mercury toxicity and poor chemical stability. Although these problems may be serious 'when the antiseptic composition is administered to the patient, The more common and common considerations caused by preservative ingredients are irritations, allergic reactions' and/or other harmful side effects. It is advantageous to be able to provide stability, effective compositions, and methods of using such compositions. Caused by the presence of preservative ingredients in such compositions (the risk of irritation and/or other harmful side effects is reduced. Conclusions of the invention a new antibiotic composition, for example for mammalian eyes, for human eyes And methods of using the composition have been found. By administering the present invention -------------------------------- (Please read the back Note: Please fill out this page again) -4- !278317 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Print A7 ------ B7______ V. Invention Description (2) When combining humans or animals, such as humans or animals The eye can obtain the therapeutic effect of the sputum, such as the prevention, control or management of the microbial infection of the eye: inflammation and/or pain & other similar circumstances, the composition is in the direction of the present invention. The composition containing the forest and the composition of the granules is essentially free of other ingredients which are preservatives. The effective amount of 4 lin can be regarded as an antibiotic when placed in a mammalian eye. In a useful embodiment, the composition The forest component has antibacterial activity. The quinoline component in the composition may have sufficient antifungal properties or activity to continuously prevent an increase in the number of molds in the composition. In fact, the 4 porphyrin The ingredients can be used as preservatives in the cost composition against mold growth. The carrier component which appears as a carrier is a carrier of the quinoline component, and if other active ingredients or general ingredients are present in the composition, it is preferably acceptable to the eye. In a very useful embodiment, the composition contains a quinine. A steroid component, a non-steroidal anti-inflammatory preparation (NSAID) component, and a carrier component effective as a carrier for the porphyrin and NSAID components. The quinoline component is as described herein as a drug that can be regarded as an antibiotic. It is present in an effective amount to reduce at least inflammation or pain when placed in a mammalian eye. The composition is preferably a porphyrin-containing porphyrin, preferably fluorinated. When the quinoline component is Ophelia A very effective composition and very effective results are obtained when the ingredients are used. Although any of the NS AID's contained in the present composition can be used, the NID component containing a carboxyl group (-COOH) is preferred. The pyrrolylpyrrole component is preferably used as the NSAID component, and the Ketorolac component is more preferred. -5- This paper scale applies to China National Standard (CNS) A4 specification mo X 297 mm) ---------------1---book--------- -- (Please read the notes on the back and fill out this page) 1278317

Printed by the Intellectual Property Office of the Ministry of Economic Affairs, the employee's consumer cooperative, the ingredients may contain one or more ingredients that are traditionally acceptable for use in eye preparations, such as tension-adjusting ingredients, buffering ingredients 'sticky ingredients, lubricating ingredients' interface. Active ingredients and analogues thereof. Preferably, the composition will have a pH of the human physiological range, for example, in the range of from about 4 to about 8.5. The present compositions may be in any form suitable for effective administration to humans or animals for treatment. The composition is preferably selected from the group consisting of a solution, a suspension, a gel, an ointment solid, and the like in a form which is very effective for administration to the eye. The carrier can be conveniently selected and/or composed so that the composition can be made in the desired form. Methods of using such compositions are included within the scope of the invention. Such methods include administering a therapeutically effective amount of a composition described herein to a human or animal, preferably a mammalian eye. This method has one or more benefits for humans or animals treated according to this method. Such benefits include, for example, prevention of control or management of microbial infections, and reduction of inflammation and/or pain. Because the compositions do not contain additional preservatives, the human or animal being treated can reduce the risk of irritation and/or other deleterious or unpleasant side effects due to the presence of preservatives. Any combination of the characteristics described herein and such characteristics are within the scope of the invention, and the characteristics of any combination are not inconsistent. These and other aspects and advantages of the present invention are set forth in the Detailed Description of the Invention and the Examples and claims. DETAILED DESCRIPTION OF THE INVENTION The present compositions contain a combination of ingredients and carrier ingredients. Importantly, the composition -6- this paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) -------------------- ——----- (Please read the notes on the back and fill in this page) 1278317

V. Description of the invention (4 Printing by the Intellectual Property Office of the Ministry of Economic Affairs, the Consumer Cooperatives = still effectively maintain the antibacterial effect of the composition, and the same: the stimulation caused by the presence of a variety or a variety of preservatives and / $:, the risk of his uncomfortable side effects. Even if the composition is substantially free of the preservative composition, it has a (4) excess of US efficacy _ (uspet) < * quasi-corrosion resistance. The composition contains (4) ingredients. I know that there are several kinds of ingredients and have been used for the system for several years. For example, the acid (4) is fine. The heart is used for the treatment of urine infection. The effective 4 4 ingredients are based on Si Junlin. There is a carboxyl group at the third position in the basic structure as follows:

The present quinoline component is preferably one which exhibits antifungal properties in the present composition. It is also effective to prevent the increase of the number I in the composition, such as white streptomyces and Aspergillus niger, in the composition of the present invention. The present quinoline component is preferably _. For example, a quinoline component can be used; for example, 9 chloromethyl _10 ♦ methyl + hexahydropyranyl) _7 oxy · 2, 3 氲 氲 i 7 Η ρ 唉 唉: alcohol [1, 2, 3 _ (^ [1,4] benzopyrene -6 acid. The composition is more preferably fluorinated. Examples of such fluorinated quinoline include Norfolk XaCin), ciprofloxacin and Ove wine Xin. _ These fluorinated quinoline ingredients are very effective in inhibiting bacteria and can be used to treat ------------------------------------ Please read the note on the back first and then fill out this page.) -7- Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed I278317 A7 —______B7_____ V. Invention Description (5) Various microbial infections of dairy eyes. The Oufuxin composition previously included for this purpose contains an added preservative such as BAK. Therefore, the quinoline is effective against eye infections, and the preservatives in the present composition may cause irritation and/or other undesirable side effects. It has now been found that 4 lining ingredients, such as auxin, are very effective in compositions which are essentially free of added ingredients as preservatives. In addition, Quelin's, such as Ovette, has been found to have sufficient anti-fungal activity and can be used as a preservative in this composition against mold contamination. As indicated above, compositions containing no preservatives but containing such u-quinion ingredients are sufficient to protect them from USPET.

The composition contains an effective amount of an η 奎琳 component having an antibacterial activity. The range of amounts can vary widely, depending, for example, on the particular type of composition employed, the particular quinoline component employed, the particular application of the composition, the frequency of use of the composition, and the like. In many cases, the compositions may contain ranges from less than about 0.03% (w/v) or greater than about 3% (w/v). The amount of the quinoline component contained in the composition is preferably in the range of about 15% (w/v) to about 5% (w/v) or about 1 · 1% (w/v). The quinoline component can be any quinoline derivative suitable for ocular administration and can have at least a portion, preferably a majority or preferably at least about 50% of the antibiotic activity of the essential quinoline in the present composition, at least in the mammalian eye. The present porphyrin component may be selected from quinoline itself or quinoline hydrate, or an ocularly acceptable salt of such quinoline, for example, including acid addition salts such as hydrochloride, maleate, pamoates, And analogs thereof, with alkali metal salts such as sodium and potassium salts, mixtures thereof and the like. —————------ Order--------- C Please read the paint on the back and fill in the purchase. -8-

1278317 A7 Λ Λ Λ ( (6) The carrier component may be selected from pharmaceutically acceptable organic and/or inorganic compounds, preferably in the presence of the composition, which is acceptable to the eye. One of the eyes of the eye can refer to the amount or concentration of the substance and the appearance of the eye tissue, that is, the substance does not cause obvious or excessive sputum when it comes into contact with the eye. The carrier component is clear to the eye. Preferably, it is preferred that each component of the composition is compatible with the other ingredients of the composition. Examples of suitable materials suitable for use in the carrier component include water, water and a solvent which can be mixed with water such as a lower grade. Alcohol or aromatic alcohol, vegetable oil, polyene, glycerin based on Vaseline, ethyl cellulose, ethyl hydrazine, carboxymethyl cellulose, polyvinylpyrrolidone, isopropyl mirstate, others traditionally used in medicine Acceptable substances and the like. The carrier component may also contain auxiliary substances such as emulsifiers, wetting agents, extenders, buffer components, acids and/or bases, tension adjusting components, interface active ingredients, thickeners, lubricating Ingredient The substance which can be used in the ophthalmic formulation and the like. Examples of the excipient which can be used arbitrarily include various kinds of polyethylene glycerol 'Jk躐' Vaseline and the like, but are not limited thereto. Suitable buffers Including inorganic buffers such as phosphate buffers, borate, buffers and the like, and organic buffers such as acetate buffers, lycopene buffer, tromethamine and the like, but not limited to The tension adjusting agent which can be used arbitrarily in the present composition includes dextrose, potassium chloride and/or sodium chloride and the like, and sodium chloride is preferred, but is not limited thereto. The acid of the composition includes boric acid, hydrochloric acid, acetic acid, other acids which are acceptable to the eye at the concentrations used, and the like. ------1-------------- Order --------- (Please read the note on the back and then fill out this page) Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing -9 - 1278317 A7 B7 7 V. Invention description (can be used arbitrarily The composition of the base fat red ## < test includes the wind sodium and / or hydroxide '〒' other metal or test The scorpion of the golden scorpion ^, the genus of the genus of the genus, the organic base, and other concentrations at the concentration used for the eye can be used for this month, succinct, and its analogues, but not limited to all The acid/test/buffer into the 6 仏 衢 衢 全 全 全 全 包括 包括 包括 包括 包括 包括 能 能 能 能 能 能 能 能 能 能 能 能 能 能 能 能 τ τ τ τ τ τ τ τ τ τ τ τ τ τ τ τ Preferably, it is preferably from about 4 to about 8.5, and is preferably white, < stone is self, and is preferably from 6 to about 8, and is preferably from about 6 8 to about 8. The composition is lacking only &,, and the mouth &mouth; the interface active ingredient includes lipoprotein cleaning system. When it is present in the composition, W夂7 T can reduce the composition and the eye fluid (tears) The surface tension between the two, 桕τ, human t knife is not limited to this. It is preferred to use a nonionic surfactant. The viscous agent which can be used arbitrarily in the composition includes carbazine (carbohydrate, cellulose derivatives such as propyl methacrylate, carboxymethylcellulose, ethyl silicate, other viscosifiers including The substances in the ophthalmic formulation and the like, but are not limited thereto. The lubricating components which can be used arbitrarily for the composition of the present invention include polyethyl propylene glycol, polyethyl acetaminophen (IV), kabab and the like, but not Limits to this. The present compositions may include an effective amount of a chelating or hiding component such as diethyldiaminetetraacetic acid (EDTA), citric acid, tartaric acid, and the like. In a useful embodiment, the composition is essentially Others arbitrarily useful in the present compositions include stabilizers such as antioxidants, such as alkali metal sulfites, ascorbic acid, and the like. The carrier components can be in a variety of different forms. In one embodiment, the carrier -1 0- This paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm! 278317 Α7

# I ::' and its composition may be a solution or suspension. In other instances, ^ can contain water with one or more accessory ingredients as referred to herein. , the two substances can be any form suitable for effective administration to the eye (these types include solutions, suspensions, ointments, gels, solids and the like. Soft palate can be regarded as a kind between suspension and gel) Intermediate type. Each type of mouthpiece of this group can be made by traditional and well-known techniques in this art. Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed in another specific example, the carrier component can be in human body temperature A clarifying substance for the preparation of a semi-solid '•gel'. There are many conventional and well-known and different I compounds which can be used as a carrier component to make the composition into a gel. A polymer system of about 40% to about 80% of poly(oxyethyl oxime) units and, and, a spoon of 20 /. to 60 / 〇 poly(oxypropylene) unit substituted alkene diamine tetra. The molecular weight of the polymer is preferably at least about 7,000 and up to about 5,000, preferably in the range of from about 7,000 to about 30, preferably. If a gel former is present, it must be in the form of a composition. An effective amount of gel. For example, such gels can be The composition may be present in a range of about 10% or more than about 50% by weight of the total carrier component. The composition may also be in the form of a blunt solid material, for example, in a solid dosage form for placement in a mammalian orbital. As a result, the composition of the composition may contain non- A biologically invasive implant, such as an implant that remains passive after release of the active ingredient or other component, or a biological invasive agent, for example, soluble or disintegrable in the tears. Solid polymers can be used in the carrier component. Such polymers include, for example, cellulose derivatives such as methyl cellulose, sodium carboxymethyl cellulose, or low alkane cellulose such as hydroxyethyl cellulose, hydroxypropyl fibers. Prime, a few propyl----------- loaded--------order--------- (please read the notes on the back and fill out this page) - 11-

1278317 A7 B7 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed 5, Invention Description (9-base cellulose and its analogues; propionate such as polyacrylate, ethyl acrylate, polypropylene decylamine, natural substances such as Ming ¥, algae, pectin, western yellow gum, daraya, red algae, acacia, gum arabic; temple powder derivatives such as temple powder, hydroxyethyl starch ether, hydroxypropyl starch, and other synthetic derivatives Such as polyvinyl alcohol, polyvinylpyrrolidone, polyethylene ethyl ether, polyethylene oxide, neutralized kabab and cream, mixtures thereof and the like. In another useful embodiment, The composition contains an effective amount of the NSAID component in addition to the quinoline component and the carrier component and can reduce inflammation and/or pain when administered to a mammalian eye, for example to avoid or treat by including glaucoma, cystic edema, uveitis Retinopathy and conjunctivitis caused by diabetes, or an inflammatory process and/or pain associated with or caused by an eye injury or injury. The NSAID may or may not contain a rebel. (-COOH) group or moiety, or a thin derivative group or moiety. In one embodiment, the NSAID component inhibits cyclooxygenase, which has two isomeric forms, designated C0X-1 and COX-2. The NSAID component is essentially a non-selective c〇x inhibitor. The NSOID component with COX-2 selectivity is also known. The NSAID components of both non-selective c〇X inhibitors and COX-2 selective inhibitors are Consistent with the present invention, the NS AID component may be selected from the group consisting of benzene dry acid, such as dicl〇fenac, flurbioprofen 'indomethacin and its analogs, Arylpyrrosis, such as celecoxib and its analogues; pyrrole valproate; and other agents that inhibit prostaglandin synthesis. A well-used NSAID component is pyrrole pyrrole, which contains propiolic acid. Part, called ketorolac and its derivatives, such as its non-toxic esters and salts. It has been applied to the China National Standard (CNS) A4 specification (210 X 297 public) at the water castle one-12-$. ) -----------Install--------Set-------I-- MW (Please read the notes on the back and fill in this page) 12783 17 A7 B7 Ministry of Economic Affairs Intellectual Property Bureau Employees Consumption Cooperatives Printed V. Inventions (10) (Waterbury) US Patent Application Boundary J. A. Calling Case No. 4,454,151 recommends the use of pyrrolizine for the treatment of certain Eye disease, the disclosure is hereby incorporated by reference. This NS AID ingredient can be used to pay for apricot machine 7, human. ^ % ^ Tianji Ding composition in mammalian eyes 'is also effective in reducing inflammation or phlegm _ <Effective concentration is present in the composition. For example, the NSAID component is preferably from 々 Λ 、, 々 0.001% (w/v) to about i 〇〇 / o (w / v), from about % 2%, π μ (W/v) Soil is preferably about 0.5% (w/v) or 1% (w/v). The composition can be prepared by conventional techniques, for example, using well-known and conventional techniques = solution/gel, suspension, and the like. More detailed information about the preparation and investment of ophthalmic formulations. j + DU _ Reference Remingtons

Pharniaceiitical Science, flute 1 ! Tience)^ 15 edition, 1489 to 15〇 is incorporated herein by reference. The king generally said that the eye of the animal used in the treatment of mammalian eyes - the treatment of the eye is less than "the person ^ only H staff, /, there is a combination of the foot of the composition to make the breasts have a good eyesight' and If the composition has an NSAm ingredient, it may also reduce the inflammation or pain of the eye. The use may include any suitable administration 2 or an effective amount of the composition for providing an effective amount of the composition to the mammalian eye. Instillation, placing an object in the eye capsule between the eyeball and the eyelid: weight and similar methods. Other traditional methods of administering the composition to the eye can also be used to allow the composition to be administered. The benefits of this application. This application should be used immediately before surgery or after trauma, that is, before the microbial infection or before the fire, /, A, fire, and / or pain, can be called For therapeutic or prophylactic ΑΑϊ-ar^, 1-I __ · ι can be used to reduce the risk of developing such infections, and may worsen the risk of inflammation or pain. - .13 - X 297 public) - -----------Install--------Book--------- MW (Please read the notes on the back and fill in Write this page) 1278317 A7 B7 V. INSTRUCTIONS (11) The dosage of the composition will of course depend on a number of factors, such as the particular application involved, the particular active ingredient or other ingredient, the active ingredient in the composition The concentration of the other ingredients, the degree of infection/inflammation/pain and the individual's response to the treatment. The dosage can be readily determined by general and known techniques to achieve the desired effect on the patient to be treated. Illustrative examples illustrate certain aspects of the invention.Examples 1 to 1 A series of compositions, compositions 1 to 1 1, are obtained by mixing the various ingredients. These compositions have the following composition 1 (please read the back first) Note: Please fill out this page) -·装---- Oufu Liquor NaCl pH Water 0.6 w/v% 0.79 w/γ% 6.4 Appropriate amount to 100% Composition 2 Order --- Ministry of Economic Affairs Intellectual Property Bureau Employee Consumption Cooperative Printed Oufu Liquor NaCl pH Water 1.0 w/v% 0.79 w/v% 6.4 Appropriate amount added to 100% -14- Stupid. This paper scale applies to China National Standard (CNS) A4 specification (21〇x 297 PCT) 1278317 A7 B7 V. Description of invention (12) Ministry of Intellectual Property, Staff, Consumer Cooperative, Printed Oufu Liquor, NaCl, EDTA, Boric Acid, PH, Oufu, Xin NaCl, EDTA, Boric Acid, pH, Calorie, Oufu, Xin NaCl, pH, Water Composition, 3 0.6 w/v%, 0.3 w/v % 0.1 wt% 1.0 w/v% 6.4 Appropriate amount to 100% Composition 4 1.0 w/v% 0.3 w/v% 0.1 wt% 1.0 w/v% 6.4 Appropriate amount to 10 0 % Composition 5 0.5 w/v % 0.6 w/v% 0.79 w/v% 6.4 Appropriate amount to 100% -15- This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) ----------- Loading -------- Order --------- (Please read the phonetic on the back first? Matters fill out this page) 1278317 A7 B7 V. INSTRUCTIONS (13 COMPOSITION 6 CARLOLINEOOL SIN NaCl pH WATER 0.5 w/v% 1.0 w/v% 0.79 w/v% 6.4 Appropriate amount to 100% combination 7 Carrotolol Oxygen NaCl EDTA Boric Acid pH Water 0.5 w/v% 0.6 w/v% 0.3 w/v% 0.1 w/v% 1.0 w/v% 6.4 Appropriate amount to 100% Composition 8 -- -----------------1—------- (Please read the phonetic transcription on the back? Please fill out this page again) Printed by the Intellectual Property Office of the Ministry of Economic Affairs Carrollol Oufu Liquor NaCl EDTA Boric Acid pH Water 0.5 w/v% 1.0 w/v% 0.3 w/v% 0.1 w/v% 1.0 w/v% 6.4 Appropriate amount to 100% This paper scale applies to Chinese national standards (CNS) A4 size (210 X 297 mm) 1278317 A7 B7 V. Description of the invention (14) Composition 9 Carrero Levonne Sina NaCl BAK L-arginine pH water 0.5 w/v% 0.3 w/v % 0.79 w/v% 0.005 w/v% 0.28 w/v% 6.4 Appropriate amount to 100% Composition 1 ο Caroluo Leofu Xin NaCl BAK Methocel® (1) Kabbah (2) pH water 0.5 w/v% 0.3 w/v% 0.79 w/v% 0.005 w/v% 0.1 w/v% 0.2 w/v% 6.4 Appropriate amount to 100% ------------ -------^----- ---- (Please read the phonetic transcription on the back? Please fill out this page again) Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing -17· This paper scale applies China National Standard (CNS) A4 specification (210 X 297 mm) 1278317 A7

V. INSTRUCTIONS INSTRUCTIONS (1S) Composition 1 1 (1) Ovosin BAK Messi® (1) Kabbah (2) Glycerol pH Water Methylcellulose 0.3 w/v% 0.005 w/v% 0.1 w /v% 0.225 w/v% 2.6 w/v% 6.5 Appropriate amount to 100% Printed by the Intellectual Property Office of the Intellectual Property Office of the Ministry of Economic Affairs (2) Polymer 2 - a series of products of the interaction of propargyl acid and pentaerythritol One of the compositions was subjected to a simple antiseptic efficacy test for each of the above compositions using white streptomyces octatus (^ 6538 and Aspergillus niger octatus (:: 16404). According to ARM T_005, the composition was based on Ph Eur-A. Standard test for /B (European Pharmacopoeia-A/B) and USP (United States Pharmacopoeia). Challenge the i-swelled composition to approximately 1 〇5 cfu/ml of test organic tissue. At appropriate intervals, bacteria The survival of the mold and the amount of mold was determined by Dey Engley gravy (DE) as a neutralization medium. The filtered DE was sufficient to neutralize the antimicrobial preparation in the composition. 9 ml per 1 ml of sample DE dilution. Then add 1 ml of this 1:10 dilution to a 0.45 μm filter and use 1 mL of saline solution / Tween® (TWEEN) 80. After cleaning for the second time with ι〇〇ml physiological saline/Tween® 80 solution, place the filter and solution on the τ § A plate and measure the bacteria and place on the SAB. The bacteria were treated in the same manner as described above, but the product was diluted 1:100 before filtration (the product of 〇·1 liters was applied to the paper size of China National Standard (CNS) A4 specification ( 210 X 297 mm) -----------Installation--------Booking-------- (Please read the notes on the back and fill out this page) 1278317 A7 B7 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed 5, Inventions (16) added to 10 ml DE). The results of these anti-corrosion tests are summarized in the following table: Composition USP Ph Eur-A Ph Eur-B 1 Passing the failure happens to pass 2 through failure failure 3 through failure happens to pass 4 through failure through 5 through failure failure through failure through failure 7 through passing by 8 through failure through 9 through through 10 through through through 11 through through through 19- ----------Install--------Book--------- (Please read the back first Note: Please fill out this page.) The paper size is applicable to China National Standard (CNS) A4 specification (210 297 297 mm). Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printed 1278317 A7 ___ B7_ V. Invention description (17) The anti-corrosion The detailed results of the efficacy test are as follows: Composition 1 2 3 4 5 6 Test organic tissue warming test interval Streptomyces aureus ATTC 6538 4X105 6 hours 2X105 9X104 1X105 8X104 8X104 1X105 24 hours 7X104 3X104 6X104 <10 8X103 2 X 103 7 days < 10 < 10 < 10 1X101 < 10 < 10 14 days < 10 < 10 < 10 < 10 < 10 < 10 28 days < 10 < 10 < 10 <;10<10<10 Aspergillus niger ATCC 16404 1X105 7 days 8X104 8X104 4X103 1X103 7X104 7X104 14 days 2X104 3X104 2X103 1X103 9X104 9X104 28 days 1X104 3X104 2X103 8X102 2X104 1X104 Composition 7 8 9 10 11 Test organic tissue warming degree Test interval Streptomyces aureus ATTC 6538 4X105 6 hours 1X105 1X105 <10 <10 <10 24 hours 3X103 1X104 <10 <10 <10 7 days <10 <10 <10 <10 <10 ;10 14 days <10 <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10 <10 Aspergillus niger ATCC 16404 1X105 7 days 2X 104 3X103 1X101 <10 1X101 14 days 2X 104 7X103 <;10<10<10 28 days 4X102 1X102 <10 <10 <1 -20- ------------装-------- Order: (Please first Read the notes on the back and fill out this page.) The paper size applies to the Chinese National Standard (CNS) A4 specification (210 X 297 mm). Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed 1278317 A7 - B7 V. Invention Description (18) The present composition passes USPET very efficiently. Especially the composition! Up to 8 does not actually contain ingredients known to be effective as preservatives, but surprisingly passes USPET, especially in the prior art compositions which already contain quinoline, such as Ophelia, already included Preservatives such as BAK. In addition, compositions i to 8 did have sufficient antifungal activity to prevent an increase in the amount of Aspergillus niger. Therefore, the quinoline contained in the composition, such as oufuxin, has sufficient mold activity to serve as a preservative against the Aspergillus niger contamination of the composition. Example 1 2 to 2 3 Another series of compositions, compositions 12 to 24, were prepared by mixing various ingredients. These compositions have the following chemical compositions. Each component includes a sufficient amount of water to achieve a weight of 1 〇〇〇/〇. Example No. Active concentration, w/v% 12 Carterian 0.5 Oufu Xin 0.3 NaCl 0.79 pH 6.4 13 Carrollol 0.5 Oufu Xin 0.3 NaCl 0.30 EDTA 0.1 Boric acid 1.0 pH 6.4 -21- This paper scale applies to China Standard (CNS) A4 specification (210 X 297 mm) -----------Package--------Set-------- (Please read the notes on the back first) Fill in this page) 1278317 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumer Cooperative Printed A7 B7 V. Description of Invention (19) Example No. Active Concentration, w/v% 14 Carterian 0.5 Ove Liquor 0.3 NaCl 0.79 BAK 0.005 pH 6.4 15 Carterian 0.5 Oufu Xin 0.3 NaCl 0.79 pH 7.4 16 Carrollol 0.5 Oufu Xin 0.3 NaCl 0.79 BAK 0.005 pH 7.6 17 Carterian 0.5 Oufu Xin 0.3 NaCl 0.79 BAK 0.005 Oxyl Alcohol (3) 0.007 pH 6.4 18 Carterian 0.5 Oufu Xinxin 0.3 NaCl 0.79 BAK 0.005 Oxyxy Alcohol (3) 0.007 pH 7.6 19 Carrollol 0.5 Oufu Xin 0.3 NaCl 0.79 BAK 0.005 Cyclodextrin (4) 0.1 pH 6.4 - 22- -------------------^--------- (please Read the phonetic transcription on the back? Please fill out this page.) The paper size is applicable to China National Standard (CNS) A4 specification (210 X 297 mm). 1278317 A7 B7 Ministry of Economic Affairs Intellectual Property Bureau employee consumption cooperative printing 5, invention description (2〇 Example sequence € Active concentration, w/v% 20 Carterian 0.5 Oufu Xinxin 0.3 NaCl 0.79 bak 0.005 Cyclodextrin (4) 0.1 pH 7.6 2 1 Carrollol 0.5 Oufu Xin 0.3 NaCl 0.79 Puri ( 5) 0.007 pH 7.6 22 ~ } Derolel 0.5 Ove Liquor 0.3 NaCl 0.79 Puri (5) 0.007 Oxyl Alcohol (5) 0.007 pH 7.6 23 Carrollol 0.5 Oufu Xin 0.3 NaCl 0.79 Puri (5) 0.007 Cyclodextrin (4) 0.1 pH 7.6 (3) Polyethylene glycerol mono(indenyl) ether (4) 7-sulfonic acid butyl ether beta-cyclodextrin (5) diazepam

The samples were tested for preservative efficacy according to the standards of Eur-A/B (European Pharmacopoeia A/B) and USP (United States Pharmacopoeia) according to ARM Τ·005. Take 1 liter per sample and test the organic tissue challenge at approximately 105 cfu/ml. Test organic tissue including Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa ATCC -23- This paper scale applies to China National Standard (CNS) A4 specification (210 X 297 mm) ---------- ----------Book--------- (Please read the phonetic on the back? Please fill out this page again) 1278317 A7 -------------B7 V. INSTRUCTIONS (21) 9〇27 'Escherichia coli ATCC 8739, Streptomyces aureus ATCC 10231 and Aspergillus niger ATCC 16404. At appropriate intervals, the survival of bacteria and molds is quantified by D E as a neutralizing medium. The filtered D E is sufficient to neutralize the antimicrobial formulation in the composition. 1 ml of each sample was diluted with 9 ml of D E. Whole Shao 10 liters were filtered through a 微米 45 micron filter and washed with ι mM phosphorus buffered physiological saline pH 5.4. After the second wash with 1 ml of phosphate buffered saline/Tween® 80, the filtrate was placed in a blood vessel to test the bacteria and the mold was tested with SAB. The test results are summarized in the table below. — II——————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————————— 12 failed through failure 13 failed through failure 14 passed through 15 through failure failed 16 through through 17 through through through 18 through through through 19 through failure through 2 0 through through 2 1 through failure failure 22 through failure failure 23 through failure failure The test results of the detailed anti-corrosion efficacy of the compositions 1 2 to 17 are as follows: -24- ------------- This paper scale applies to the Chinese National Standard (CNS) A4 specification (210 X 297 PCT) 1278317 Ministry of Economic Affairs Intellectual Property Bureau Staff Consumption Cooperative Printed A7 B7 V. Invention Description (22) Composition 12 13 14 15 16 17 Test Organic Group Test Weaving Degree of Interval Golden Key bacterium 6 hours 2Χ105 2Χ105 4 3Χ105 &lt ; 10 1 ATCC 6538 24 hours 2 X 105 2 X 105 < 10 3 X 105 < 10 < 10 5X105 7 days < 10 2 X 101 < 10 < 10 < 10 < 10 14 days < 1 0 < 10 < 10 < 10 < 10 < 10 28 days < 10 < 10 < 10 < 10 < 10 < 10 Pseudomonas 6 hours < 10 < 10 < 10 <10 <10 <10 ATCC 9027 24 hours <10 <10 <10 <10 <10 <10 <10 3X105 7 days <10 2 X 101 <10 <10 <10 <10 ; 10 14 days < 10 < 10 < 10 < 10 < 10 < 10 28 days < 10 < 10 < 10 < 10 < 10 < 10 E. coli 6 hours 6 Χ 101 5 Χ 101 < 10 5Χ101 <10 <10 ATCC 8739 24 hours 5Χ102 <10 <10 <10 <10 <10 5 X105 7 days <10 <10 <10 <10 <10 <10 <10 14 days <10 <10 <10 <10 <10 <10 28 days <10 <10 <10 <10 <10 <10 <10 Candida albicans 7 days 1Χ105 2Χ105 <lt ;10 3Χ105 <10 <10 <10 ATCC 10231 14 days 1 X 105 2 X 105 <10 1 X 105 <10 <10 3 X105 28 days 8 X 104 9 X 104 <10 9 X 104 <10 <10 Aspergillus oryzae 7 days 6Χ104 6Χ104 3Χ101 7Χ104 <10 3Χ101 ACTT16404 14 days 4 X 104 3 X 104 4 6 X 104 1Χ102 <10 1Χ105 28 days 3 X 104 3 X 104 <10 4 X 104 &l t;10 <10 -25- -------------------Set-------->^AW. (Read the phonetic on the back first? Please fill out this page again. This paper size applies to China National Standard (CNS) A4 specification (210 X 297 mm). 1278317 Ministry of Economic Affairs Intellectual Property Office Staff Consumer Cooperative Printed A7 B7 V. Invention Description (23) Some of the composition Some specific examples, compositions 12 to 15 , do not include ingredients that are effective as preservatives. However, these compositions do pass USPET. Furthermore, although compositions 12 to 15 did not pass the European Pharmacopoeia's preservative efficacy test, they did have sufficient anti-fungal activity to prevent an increase in the number of white sputum and black scorpion emblems. The p-quinone in the composition, Ove wine, has sufficient anti-fungal activity and can be used as a preservative for the composition against white streptomyces and Aspergillus niger. In addition, compositions containing diazepam 2, 2 2 and 2 3 are known to be effective preservatives in ophthalmic formulations. However, these compositions have not passed the European Pharmacopoeia's preservative efficacy test. Example 2 4 to 3 3 Compositions 1 to 8, 12 and 15 in solution form were administered to human eyes infected with microorganisms. Each eye is administered with about 1 to 2 drops of each composition containing from about 25 to 50 microliters of the composition. Drop 3 to 4 times a day. One week after these administrations, each treated eye was free of microbial infection. Example 3 4 to 3 9 Compositions 5 to 8, 12 and 15 were administered to the eyes with surgical trauma. Each eye sees some degree of inflammation and becomes a source of some pain before administration. Each eye is administered with about 1 to 2 drops of each composition containing about 25 to 5 microliters of the composition. Drop 3 to 4 times a day. One week after these administrations, each treated eye has no inflammation and is no longer a source of pain. In addition, each eye remains unaffected by microbes. -26- This paper scale applies to China National Standard (CNS) A4 specification (210 297 297 mm) -------------------^-------- - (Please read the note on the back and then fill out this page) 1278317 A7 B7__ V. INSTRUCTIONS (24) When the present invention is described in terms of specific examples and specific examples, it must be understood that the invention is not limited thereto and may be Different examples are made within the scope of the patent application. (Please read the phonetic transcription on the back side and then fill out this page.) Printed by the Consumer Intellectual Property Office of the Ministry of Economic Affairs -27- This paper scale applies the Chinese National Standard (CNS) A4 specification (210 X 297 mm).

Claims (1)

Α8 Β8 C8 D8 Ι27^3άί!ΐ6〇5 Patent Application Replacement of Chinese Patent Application (June 1995) VI. Patent Application 1. An ophthalmic pharmaceutical composition comprising: an effective amount of quinoline component, when The composition can be regarded as an antibiotic when placed in a mammalian eye; an effective amount of an NSAID component which reduces inflammation or pain when the composition is placed on a mammalian eye; and an effective amount of a carrier component which can be used as a quinoline component in the composition and A carrier of an NSAID component which is ocularly acceptable and which is substantially free of other ingredients which can be considered as preservatives. 2. The composition according to claim 1, wherein the NSAID component is a carboxyl group-containing NSAID component. 3. The composition of claim 1, wherein the carrier component is selected such that the composition forms a form selected from the group consisting of a solution, a suspension, a gel, an ointment, and a solid. 4. The composition according to claim 1, wherein the quinoline component is a halogenated p-quinone component. 5. The composition according to claim 4, wherein the NSAID component is a carboxyl group-containing NSAID component. 6. The composition according to claim 1, wherein the Junlin component is a fluorinated P-quinone component. 7. The composition according to claim 6 wherein the NSAID component is a carboxyl group-containing NSAID component. 8. The composition according to claim 1, wherein the quinoline component is an ingredient of ofloxacin. 9. The composition according to item 8 of the patent application scope, wherein the NSAID component is the paper size applicable to the Chinese National Standard (CNS) A4 specification (210 X 297 mm) 1278317 A8 B8 C8 D8 VI. Application for Patent Park's — The NSAID component of the carboxyl group. 10. The composition of claim 1, wherein the NSAID component is a ketorolac component. 11. A composition according to claim 10, wherein the carrier component is selected such that the composition is formed in a form selected from the group consisting of liquids, suspensions, gels and ointments. 12. The composition according to claim 10, wherein the quinoline component is a quinone p-quinone component. 13. The composition of claim 10, wherein the quinoline component is a gasified p-quinone component. 14. A hydrate according to claim 10, wherein the quinoline component is an ingredient of ofloxacin. 15. Use of a composition according to any one of claims i, 3, 4, 8, 1 and 14 of the patent application for the preparation of a medicament for the treatment of mammalian eye. 16. A pharmaceutical composition for ophthalmology, comprising: an effective amount of a quinoline component, which can be regarded as an antibiotic when the composition is placed in a mammalian eye, and the + component of the composition has antifungal activity; An effective amount of a carrier component which acts as a carrier for the quinoline component of the composition, which is acceptable for the eye, which composition is substantially free of other ingredients which can be considered as preservatives. 17. The composition according to claim 16 wherein the carrier component is selected such that the composition forms a SS standard selected from the group consisting of solutions, suspensions, gels, ointments, and solids. _ Α 4 specifications (21 () χ 297 public love 5 a ' ~------ 1278317 A8 B8 C8 D8 Sixth, the scope of the application for patent scope. 18. The composition of claim 16 wherein the quinoline component is a halogenated quinone component. 19. The composition of claim 16, wherein the porphyrin component is a fluorinated quinoline component. 20. The composition according to claim 16 wherein the porphyrin component is ofloxacin component 0. 21. The composition according to claim i of claim 6 further comprising an additional effective amount of active ingredient A therapeutic effect may be provided when placed in a mammalian eye, and the carrier component is sufficient to serve as a carrier for the additional active ingredient. The composition according to claim 2, wherein the additional active ingredient is an NSAID The ingredients are in an amount sufficient to reduce inflammation or pain when the composition is placed on a mammalian eye. 23. The composition according to claim 22, wherein the NSAID component is a carboxyl group-containing NSAID component. 24. The composition according to claim 22, wherein the Nsaid component is a Carterian component. 25. The composition according to claim 24, wherein the quinoline component is a oufuxin component. * 26. Use of a composition according to any one of claims 16, 17, 20, 24 and 25 for the preparation of a medicament for the treatment of mammalian eye. -3 - This paper size is applicable to China National Standard (CNS) Α4 specification (210 X 297 mm) 裴